ADMINISTRATION OF A BIOASSAY PROGRAM

Administering a bioassay program requires that the policies, procedures, materials, support facilities, and staff be in place to enable a bioassay program to commence. Among the administrative items to address are the following:

• management policy requiring participation in bioassay program by appropriate workers (may be part of an overall radiation protection policy),

• implementing procedures (e.g., criteria for who should participate, scheduling, sample kit instructions, sample kit issue/receipt, follow-up to unsuccessful sample or measurement attempts, data-handling),

• arrangements with appropriate analytical laboratories, including specifications of analysis sensitivity, processing times, reporting requirements, and quality assurance provisions,

• onsite support facilities (e.g., sample kit storage locations, sample kit issue/collection stations, measurement laboratory facilities, equipment maintenance),

• staff selection, qualification, and training,

• total committed effective dose from all intakes during a year,

• committed equivalent dose to organs or tissues of concern from all intakes during a year,

• magnitude of intake for each radionuclide during a year,

• data necessary to allow subsequent verification, correction, or recalculation of doses, and

• gestation period equivalent dose to the embryo/fetus from intake by the mother during the entire gestation period.

Recommendations for testing criteria for radiobioassay laboratories are in ANSI N13.30. These recommendations include calculational methods and performance criteria for bias, precision, and testing levels. The establishment of minimum detection capability must be driven by programmatic needs, ideally related to some concept of a minimum detectable dose, rather than as a single magnitude number.

Some sites have established brief flyers or brochures describing their bioassay measurements.

These may be distributed to workers during classroom training, upon notification of scheduled measurements, or at the time of the measurement or sample.

The choice of the measurement technique, or of a combination of techniques, depends on the radioisotopes, physicochemical forms, and exposure pathway.

Because of the wide range of chemical and physical forms of uranium, an appropriate bioassay program is one that does not rely on assumed transportability and will provide data from which radiation dose can be calculated that will not be dependent on the chemical form. This will normally require both in vivo and in vitro bioassay. If the uranium being handled has been shown to be of medium to high

transportability, then the bioassay program must be designed to demonstrate that 3 µg U/g kidney has not been exceeded.

Uranium Type S materials cannot be effectively detected at the levels listed in ICRP Publication 54 by ordinary methods available for either lung in vivo counts or urinalysis. This is shown by the fact that the derived investigation level (DIL) (based on 0.3 ALI as per ANSI/HPS 1995) was 0.06 pCi L^-1,which is below the MDA suggested as reasonable for routine uranium alpha urinalysis (0.1 pCi L^-1)in the standard.

A combination of urine and fecal sampling for Type S materials will allow for adequate detection of uranium.

5.5.1 In Vivo Monitoring

The scheduling and measurement process for obtaining in vivo measurements is usually

straightforward. Workers are scheduled for the measurements and results are available shortly after the

not completed or a worker fails to show.Occasionally, workers are found who are claustrophobic when placed inside in vivo counter cells. Leaving the cell door partially open may help reduce some of the anxiety, but will also likely compromise the low background for which the system is designed.

Many workers want to know the results of their measurements. While a simple statement by the in vivo measurement technician may be adequate, a form letter stating that results were normal (or showed no detection of any of the nuclides of concern) can provide permanent verification. If results are not normal, a form letter can also be used to explain what happens next.

In vivo analysis is most useful for characterizing inhalation exposure of Type M or S compounds of uranium by lung counting. MDAs are generally not sufficiently low to provide reliable information about systemic distribution of soluble uranium at occupational levels. The ²³⁵U decays with emission of an energetic (186-keV) photon in high abundance that is used for in vivo monitoring of enriched uranium workers. The other long-lived uranium isotopes emit only low yields of low-energy photons (<60 keV), which are easily attenuated by body tissue and have limited usefulness for in vivo analysis. Internal exposures to aged depleted uranium can be measured in vivo by taking advantage of several photons of moderate energy (63-93 keV) emitted by the ^234mPa daughter of ²³⁴Th, which are both short-lived daughters of ²³⁸U.

An important aspect of any in vivo measurement program is the calibration and verification testing of the measurement equipment. In vivo measurement results are highly dependent on the determination of a background result. Likewise, calibration using known activities in appropriate phantoms is also

important.

5.5.2 Urine Sampling

Urine sampling programs can be effectively administered using either workplace or home collection protocols. Workplace sampling protocols must determine whether adequate precautions are taken to prevent external contamination of the sample by levels of activity well below the detection capabilities of friskers and workplace monitors. Home collection protocols have the advantage of being sufficiently removed from the workplace to render essentially nonexistent the potential of very low-level contamination of the sample from external sources of uranium. Avoidance of very minor external contamination of the samples is extremely important due to the dosimetric implications of uranium in urine.

Large-volume urine samples are necessary for bioassay monitoring due to the very small urinary excretion rates. Ideally, 24-hour total samples would be preferred; however, such samples often impose substantial inconvenience on workers, resulting in noncompliance with the instructions. As an alternative, total samples can be simulated by either time-collection protocols or volume normalization techniques.

One method of time-collection simulation (NCRP 1987b; Sula et al. 1991) is to collect all urine voided from 1 hour before going to bed at night until 1 hour after rising in the morning for two consecutive nights. This technique has been reviewed with regard to uranium (Medley et al. 1994) and found to underestimate daily urine excretion by about 14%. Such a finding is not unexpected, since the time span defined by the protocol is likely to be about 18 to 22 hours for most people.

The volume normalization technique typically normalizes whatever volume is collected to the ICRP Reference Man daily urine excretion volume of 1400 mL. Reference Woman excretion (1000 mL/d) may be used for gender-specific programs. As a matter of practicality, routine monitoring programs do not usually use gender as a basis of routine data interpretation, particularly since results are anticipated to be nondetectable under normal conditions.

A third method calls for collection of a standard volume (e.g., 1 liter) irrespective of the time over which the sample is obtained. This method uses the standard volume as a screening tool only for routine monitoring. It does not attempt to relate measured routine excretion to intake, relying on well-defined and timely supplemental special bioassay to give true or simulated daily excretion rates.

The most common sample collection containers are 1-liter polyethylene bottles. Although glass bottles are also used, they pose additional risks of breakage. Wide-mouthed bottles are preferred for convenience and sanitation. The number of bottles included in the kit should be appropriate to the protocol; for a total 24-hour protocol, as much as 3 liters can be expected. Special provisions, such as a funnel or transfer cup, may improve the esthetics of sample collection and provide for added worker cooperation.

Some concerns can exist with length of sample storage before analysis. Storage may come from delays before batching samples in-house or due to transportation times to an offsite laboratory. The longer a sample stands, the more chemical and biological change it can undergo, typically manifesting itself as sedimentation and plate-out on container walls. While samples can be preserved by acidification or freezing, good radiochemistry techniques should ensure essentially complete recovery of any plate-out or sediment. Samples sent offsite for analysis can be preserved with acid, but this method imposes hazardous material shipping requirements. Freezing samples can preserve them, but plate-out and sedimentation upon thawing should still be expected.

Precautions are necessary if a lab uses an aliquot for analysis and extrapolates the aliquot result to the total sample. The aliquoting procedure should be tested using spiked samples to determine if it is representative.

A quality control (QC) verification program should exist for laboratory analyses, including use of known blank samples and samples spiked with known quantities of radioactivity. Ideally, the samples should not be distinguishable by the analytical laboratory from actual worker samples. The number of QC verification samples may range from 5% to 15% of the total samples processed by a large-volume program;

a small program focused on submittal of special samples following suspected intakes may have a much higher percentage of controls. An additional QC provision may be to request the analytical lab to provide results of their in-house QC results for independent review.

There are no standard or regulatory requirements for bioassay sample chain-of-custody provisions, nor has there been consensus on their need. Tampering with samples has not been a widely reported or suspected problem. Site-specific chain-of-custody requirements should be based on balancing the need with the resources required to implement them. Some sites have no chain-of-custody requirements associated with bioassay sample collection. At other sites, a simple seal placed on a sample container following collection by the subject worker is an effective means of providing a small degree of chain-of custody. At the more complex level would be strict accountability requiring signature of issue, certification of collection, and signature of submittal.

Procedures describing details of the bioassay program should be documented. These procedures should include a description of sample collection, analysis, calibration techniques, QC, biokinetic modeling, and dose calculational methods used.

5.5.3 Fecal Sampling

Fecal analysis is most useful in the first few days after a known acute exposure, since a large fraction of either an ingestion or inhalation deposition is excreted in feces. Chronic inhalation exposures to Type M or S uranium can also be characterized by fecal analysis, since a large fraction of the material clears to the GI tract and is eliminated in feces. Urinalysis is the only reliable method for determining inhalation exposures to Type F uranium and for monitoring the excretion of systemic uranium. It also provides complementary information, which, when used with in vivo or fecal monitoring results, contributes to greater accuracy in internal dose assessments. Because urinalysis is generally less disruptive to work schedules than in vivo monitoring and more acceptable to workers than fecal monitoring, it occupies a prominent place in most uranium bioassay programs.

Fecal analysis is often more likely to detect exposure to highly insoluble Type S material than urinalysis. The ratio between the fecal excretion level per day and the urine excretion level per day is greater than 7, as calculated for a 90-day sampling interval. All action levels are above the typically attainable MDA for fecal analysis of 0.1 pCi per L (ANSI/HPS 1996). Thus, it is recommended that facilities that have a significant Type S uranium exposure potential should have fecal analysis capabilities available to them, unless they have urinalysis methods that have MDAs well below the 0.1 pCi per sample (ANSI/HPS 1995).

A fecal sampling program must be designed to optimize worker cooperation, whether collecting samples at home or in the workplace. Since the frequency of fecal voiding varies greatly from person to person, the sample collection program must be adaptable. Flexibility in sample dates is important. It is suggested that when a fecal sample is required, the worker be provided with a kit and instructed to collect the sample, noting the date and time of voiding on the sample label. This practice can reduce the

likelihood of unsuccessful samples. If multiple samples are required (for example, to collect the total early fecal clearance following an acute inhalation exposure), the worker may be given several kits and told to collect the next several voidings, noting the date and time of each.

Since the total fecal voiding should be collected, thought must be given to the kit provided. Fecal sampling kits can be obtained from medical supply companies or designed by the site. A typical kit might include a large plastic zipper-closure bag to hold the sample, placed inside a 1- to 2-liter collection bucket with a tight-fitting lid. The bucket and bag can be held in place under a toilet seat by a trapezoid-shaped bracket with a hole through it sized to hold the bucket. After sample collection, the zipper bag is sealed, the lid is snapped tight on the bucket, and the bucket placed in a cardboard box.

Following collection, the provisions for sample handling, control, analytical, and QC are similar to those described above for urine samples. One particular concern for fecal analysis is the potential

difficulty of dissolving Type S uranium in the fecal matrix. While nitric acid dissolution may be adequate, enhanced digestion using hydrofluoric acid may be preferred.

5.5.4 Conditions for Adjustments of Action Levels

When workers are potentially exposed to other radiation sources or toxic agents, the action levels should be reevaluated. Since uranium has both chemical and radiological toxicity characteristics, urinalysis results should be interpreted both in terms of mass and radioactivity to ensure that the most appropriate set of action levels is used (ANSI/HPS 1995).